Genetic remnants of an ancient infection indicate the mysterious Denisovans, not humans, are Neanderthals’ closest cousins

Humans and Neanderthals are close cousins. So close, in fact, that some researchers argue the two hominids might actually be members of the same species. But a few years ago, anthropologists discovered a mysterious new type of hominid that shook up the family tree. Known only from a finger fragment, a molar tooth and the DNA derived from both, the Denisovans lived in Asia and were contemporaries of Neanderthals and modern humans. And they might have been Neanderthals’ closest relatives. A recent study of virus “fossils” provides new evidence of this relationship.

Hidden inside each, embedded in our DNA, are the genetic remnants of viral infections that afflicted our ancestors thousands, even millions of years ago. Most known virus fossils are retroviruses, the group that includes HIV. Consisting of a single strand of RNA, a retrovirus can’t reproduce on its own. After the retrovirus invades a host cell, an enzyme reads the RNA and builds a corresponding strand of DNA. The virus-derived DNA then implants itself into the host cell’s DNA. By modifying the host’s genetic blueprints, the virus tricks the host into making new copies of the retrovirus.

But sometimes the host fails to make new copies of the virus. If this happens in a sperm or egg cell, the virus DNA becomes a permanent part of the host’s genome and is passed on from generation to generation. These virus fossils have distinct genetic patterns that scientists can identify during DNA analyses. After the Human Genome Project was finished in 2003, researchers estimated that about 8 percent of human DNA is made up of virus DNA.

With that in mind, a team led by Jack Lenz of the Albert Einstein College of Medicine in New York used virus fossils as a way to sort out the degree of relatedness among humans, Neanderthals and Denisovans. The researchers discovered that most of the ancient viruses found in Denisovans and Neanderthals are also present in humans, implying that all three inherited the viral genetic material from a common ancestor. However, the team also found one virus fossil present in Neanderthals and Denisovans that is missing in humans. This implies Denisovans are more closely related to Neanderthals than we are, the researchers reported in Current Biology. Humans must have split off from the lineage leading to Neanderthals and Denisovans; then the infection occurred, and then Neanderthals and Denisovans split from each other.